Abstract The spinothalamic tract has long been known as a primary conductor of nociceptive information, with its anatomical and physiological understanding evolving over centuries of research. This comprehensive review traces the history of the spinothalamic tract beginning with Brown-Sequard’s 1860 report of contralateral analgesia following a hemisection of the spinal cord. As clinical and surgical interventions, such as cordotomies have advanced, so did our understanding of the spinothalamic tract’s function and anatomy. The spinothalamic tract’s role as a crossed pathway conducting pain and temperature sensations was solidified by the mid-20th century. However, intricate details of its somatotopic arrangement, anatomical distributions and sensory modalities were further refined by subsequent studies. Additionally, by examining complications of cordotomies, such as Ondine’s Curse (central hypoventilation syndrome), urinary and autonomic dysfunction, motor weakness and late-onset new pain, the intricate relationships between the spinothalamic tract, the ascending and descending reticular tracts, the spinocerebellar tracts and other vital pathways governing micturition and autonomic functions were discovered.